纵向血浆代谢组学指导食管鳞状细胞癌化疗免疫治疗的动态风险评估与饮食调节
Longitudinal Plasma Metabolomics Guides Dynamic Risk Assessment and Dietary Modulation for Esophageal Squamous Cell Cancer Chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
PD-L1 和 HLA-I 类表达状态及其在食管小细胞癌中的治疗意义
英文原题：PD-L1 and HLA-class I expression status and their therapeutic implication in oesophageal small-cell carcinoma.
查看英文原题
PD-L1 and HLA-class I expression status and their therapeutic implication in oesophageal small-cell carcinoma.
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研究概要
鉴于相当一部分（40%）患者表现为 PD-L1 CPS 1，同时保留 HLA-I 类表达且 TIL 水平高，PD-1/PD-L1 通路是食管小细胞癌的潜在治疗靶点。
中文摘要
目的
食管小细胞癌是一种罕见且高度侵袭性的食管癌亚型，预后极差。为探索免疫疗法的潜在应用，我们调查了食管小细胞癌中程序性死亡配体 1（PD-L1）、人白细胞抗原（HLA）I 类表达状态及TIL（肿瘤浸润淋巴细胞）程度。 方法与结果：评估 10 例纯小细胞癌和 5 例混合性神经内分泌-非神经内分泌肿瘤（MiNEN）的 PD-L1 和 HLA-I 类表达。采用综合阳性评分（CPS）和肿瘤比例评分（TPS）评估 PD-L1，并对错配修复（MMR）蛋白进行免疫组化。PD-L1 免疫组化显示，9 例（60%）CPS≥1，5 例（33%）CPS≥10，5 例（33%）TPS≥1。CPS≥1 患者总生存期显著长于 CPS<1 患者。5 例（33%）存在 HLA-I 类缺失（>50% 肿瘤细胞），与 PD-L1 表达状态无显著相关。5 例 MiNEN 中，3 例的小细胞癌成分 HLA-I 类表达降低。HLA-I 类缺失与更高 TNM 分期和较低 TIL 水平显著相关。未观察到 MMR 缺陷。
结论
相当一部分病例（40%）存在 PD-L1 CPS≥1，同时 HLA-I 类表达保留且 TIL 水平高，提示 PD-1/PD-L1 通路可能是食管小细胞癌的治疗靶点。
展开英文摘要原文
AIMS: Oesophageal small-cell carcinoma is a rare and highly aggressive subtype of oesophageal cancer with a dismal prognosis. To explore the potential applicability of immunotherapy, we investigated the expression status of programmed death ligand 1 (PD-L1) and human leukocyte antigen (HLA)-class I and the degree of tumour-infiltrating lymphocytes (TILs) in oesophageal small-cell carcinoma. METHODS AND RESULTS: PD-L1 and HLA-class I expression levels were evaluated in 10 pure small-cell carcinomas and five mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). The combined positive score (CPS) and tumour proportion score (TPS) were used for PD-L1 assessment. Immunohistochemistry for mismatch repair (MMR) proteins was also performed. PD-L1 immunohistochemistry demonstrated CPS 1 in nine (60%), CPS 10 in five (33%), and TPS 1 in five (33%) cases. Overall survival was significantly longer in patients with CPS 1 than in those with CPS <1. HLA-class I deficiency (>50% tumour cells) was noted in five cases (33%), with no significant correlation with PD-L1 expression status. Among the five MiNENs, HLA-class I expression was decreased in the small-cell carcinoma component of three cases. HLA-class I deficiency was significantly associated with higher TNM stage and reduced TIL levels. MMR deficiency was not observed in any case. CONCLUSION: Given that a significant subset (40%) exhibited PD-L1 CPS 1 with preserved HLA-class I expression and high levels of TIL, the PD-1/PD-L1 pathway is a potential therapeutic target for oesophageal small-cell carcinoma.
论文信息
- 作者
- Yamashita S、Abe H、Yamashita H、Yagi K、Seto Y、Ushiku T
- 单位
- Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.Japan
- 期刊
- Histopathology2023 Aug
- 原文标识
- PubMed 37071391 · DOI 10.1111/his.14924